Phase 2 Discovery is developing a synthetic melatonin analog (PD6735) for the treatment of jet lag. No medications are currently approved by the FDA for treatment of jet lag. Medications used "off-label" for jet lag possess undesired side effects. PD6735 is being developed as a safe and effective treatment for jet lag that lacks the side effects of commonly used medications. Initial clinical studies indicate that PD6735 is safe and well tolerated by humans through the maximal dose tested, 100 mg. PD6735 produced a dose-response improvement in re-adaptation to a simulated 9 hour phase shift in a double blind, placebo controlled cross over study (n=8). PD6735 also produced a dose-response improvement in sleep latency in subjects with primary insomnia in a double blind, placebo controlled cross over study (n=40). The goal of this Phase 1 application is to evaluate the feasibility of using PD6735 to reduce the symptoms of jet lag in actual air travel. Our Specific Aims are: Aim 1: Evaluate the ability of PD6735 to reduce symptoms of jet lag in long distance air travelers. Travelers (n=90) will receive PD6735 25 mg or placebo for 4 days during and after a multi-time zone flight in a randomized, placebo-controlled, double blind study. The travelers will complete the Columbia Jet Lag Scale and visual analog measures of jet lag symptom severity for 5 days during and after a multi-time zone flight; flights may be east-bound (phase advance) or west-bound (phase delay) and must cross at least 5 time zones. The rating scales will be collected, scored and statistically analyzed. Prediction: PD6735 at a dose of 25 mg for 4 days will produce a significant improvement jet lag symptoms when compared to placebo. Specific Aim 2: Evaluate the safety of PD6735 when used by long distance air travelers. Safety measures, including vital signs, electrocardiogram and clinical laboratory tests will be performed at subject enrollment and completion of the jet lag study proposed in Aim 1. Clinical adverse events, solicited and by spontaneous report, will be recorded. Prediction: PD6735 at a dose of 25 mg for 4 days will be well tolerated with a frequency of adverse events not different from placebo. [unreadable] [unreadable] [unreadable] [unreadable]